An Extension Study of Iron Chelation Therapy With Deferasirox (ICL670) in β-thalassemia Patients With Transfusional Iron Overload

• ClinicalTrials.gov Identifier: NCT00171210
• Recruitment Status: Completed
• First Posted: September 15, 2005
• Results First Posted: May 2, 2011
• Last Update Posted: May 30, 2011
• Sponsor: Novartis Pharmaceuticals
• Information provided by: Novartis

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Transfusional Iron Overload in β-thalassemia
• Intervention: Drug: Deferasirox
• Enrollment: 506

Participant Flow

Recruitment Details	This study is an extension of core study (NCT0061750). 555 participants were treated with Deferasirox (ICL670) in the core and/or extension study. In the core study, 296 participants were treated with ICL670 and 259 participants were treated with Deferoxamine(DFO).
Pre-assignment Details

Arm/Group Title	Crossover	ICL670
Arm/Group Description	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Period Title: Overall Study
Started	259	296
STARTED EXTENSION STUDY	259	247
Completed	190	181
Not Completed	69	115
Reason Not Completed
Adverse Event	16	27
Abnormal laboratory value(s)	6	3
Abnormal test procedure result(s)	0	1
Unsatisfactory therapeutic effect	11	15
Protocol Violation	0	2
Withdrawal by Subject	32	30
Lost to Follow-up	1	0
Administrative problems	1	1
Death	2	3
Stopped at end of core	0	32
Stopped at end of extension 1	0	1

Baseline Characteristics

Arm/Group Title		Crossover	ICL670	Total
Arm/Group Description		Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.	Total of all reporting groups
Overall Number of Baseline Participants		259	296	555
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	259 participants	296 participants	555 participants
		18.3 (9.82)	17.1 (9.46)	17.7 (9.64)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	259 participants	296 participants	555 participants
	Female	125 48.3%	156 52.7%	281 50.6%
	Male	134 51.7%	140 47.3%	274 49.4%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	259 participants	296 participants	555 participants
Black or African American		1	2	3
White		225	263	488
Oriental		10	9	19
Other		23	22	45

Outcome Measures

1. Primary Outcome

Title	Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event
Description	Adverse events results are based on preferred terms with at least 7% of participants in any group.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	259	296
Measure Type: Number; Unit of Measure: Participants
Pyrexia	109	113
Cough	85	110
Headache	81	84
Diarrhoea	73	69
Vomiting	61	75
Influenza	65	70
Abdominal pain	59	75
Nasopharyngitis	56	73
Nausea	52	63
Oropharyngeal pain	50	62
Pharyngitis	57	55
Back Pain	49	59
Abdominal pain upper	52	52
Rhinitis	45	52
Bronchitis	41	45
Arthralgia	39	45
Upper respiratory tract infection	32	52
Transfusion reaction	36	34
Blood creatinine increased	22	47
Gastroenteritis	31	37
Asthenia	31	31
Rash	24	34
Tonsillitis	22	30
Fatigue	22	29
Pain in extremity	21	30
Acute tonsillitis	21	29
Dyspepsia	17	21
Urinary tract infection	14	23
Urticaria	14	23
Toothache	14	22
Sinusitis	13	22
Cholelithiasis	11	23

2. Secondary Outcome

Title	Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by Liver Biopsy
Description	Mean absolute change of LIC from start of Deferasirox (ICL670) treatment to the end of study assessed by liver biopsy. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw).
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC Biopsy data at Start of ICL670 treatment and End of Study.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	95	220
Mean (Standard Deviation); Unit of Measure: mg Fe/g dw
	-2.4 (8.23)	-4.1 (10.31)

3. Secondary Outcome

Title	Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by SQUID
Description	Mean absolute change in LIC from start of Deferasirox (ICL670) treatment to the end of the study assessed by Superconducting Quantum Interfering Device (SQUID) measurement used as a non-invasive alternative to Biopsy for pediatric participants. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw).
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC SQUID data at Start of ICL670 treatment and End of Study.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	34	44
Mean (Standard Deviation); Unit of Measure: mg Fe/g dw
	-0.5 (5.34)	-0.7 (4.03)

4. Secondary Outcome

Title	Long-term Effect of Treatment With ICL670 on the Changes in Serum Ferritin Levels From Start of ICL670 Treatment to End of Study
Description	Mean Absolute Change in serum ferritin (ug/L) from start of treatment with Deferasirox (ICL670) to end of study taking into account the therapeutic goal which will either be to maintain iron balance or to induce negative iron balance. End of study taken as the mean of, at most, the last three available results after start of treatment with ICL670.
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	259	296
Mean (Standard Deviation); Unit of Measure: μg/L
	-122.1 (1406.77)	-527.8 (1852.12)

5. Secondary Outcome

Title	Change in Surrogate Marker: Serum Transferrin From Start of Treatment With ICL670 to End of Study
Description	Measurement of the relative change in percent of potential surrogate marker: Serum Transferrin (g/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Transferrin at the End of Study-Serum Transferrin at Start of ICL670)/Serum Transferrin at Start of ICL670*100.
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	259	296
Mean (Standard Deviation); Unit of Measure: Percent change
	7.7 (16.3)	7.0 (14.78)

6. Secondary Outcome

Title	Change in Surrogate Marker: Serum Iron From Start of Treatment With ICL670 to End of Study
Description	Measurement of the relative change of potential surrogate markers: Serum Iron (µmol/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Iron at the End of Study-Serum Iron at Start of ICL670)/Serum Iron at Start of ICL670*100.
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	259	296
Mean (Standard Deviation); Unit of Measure: Percent change
	1.5 (29.99)	10.3 (39.07)

7. Secondary Outcome

Title	Change in Surrogate Marker: Transferrin Saturation From Start of Treatment With ICL670 to End of Study
Description	Measurement of the relative change of potential surrogate marker: Transferrin Saturation (Percent) from start of treatment with Deferasirox (ICL670) to end of study. (Transferrin Saturation at the End of Study-Tranferrin Saturation at Start of ICL670)/Transferrin Saturation at Start of ICL670*100.
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	259	296
Mean (Standard Deviation); Unit of Measure: Percent change
	-5.4 (27.06)	3.4 (36.17)

8. Secondary Outcome

Title	Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy
Description	Measurement of median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through biopsy. Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw).
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC Biopsy data at Start of ICL670 treatment and End of Study.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	95	220
Median (Full Range); Unit of Measure: mg Fe/g dw
	-2.8; (-24.0 to 18.4)	-3.2; (-34.7 to 31.4)

9. Secondary Outcome

Title	Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy
Description	Relative change in liver iron content (LIC) as measured by biopsy and calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value.
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC Biopsy data at Start of ICL670 treatment and End of Study.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	95	220
Median (Full Range); Unit of Measure: percent of start value
	-25.4; (-97.6 to 314.6)	-26.0; (-100.0 to 581.5)

10. Secondary Outcome

Title	Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by SQUID
Description	Measurement of the median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through Superconducting Quantum Interfering Device (SQUID). Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw).
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC SQUID data at Start of ICL670 treatment and End of Study.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	34	44
Median (Full Range); Unit of Measure: mg Fe/g dw
	-1.1; (-14.1 to 18.1)	-1.6; (-8.7 to 12.0)

11. Secondary Outcome

Title	Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study as Measured by SQUID
Description	Relative change in liver iron content (LIC) measured by Superconducting Quantum Interfering Device (SQUID), calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value.
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC SQUID data at Start of ICL670 treatment and End of Study.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	34	44
Median (Full Range); Unit of Measure: percent of start value
	-20.8; (-84.4 to 517.1)	-33.0; (-87.0 to 218.2)

12. Secondary Outcome

Title	Change of Total Body Iron Excretion Rate (TBIE) From Start of ICL670 Treatment to the End of Study
Description	Median change in TBIE (mg/kg/day) from start of treatment with Deferasirox (ICL670) to end of study.
Time Frame	Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.

Arm/Group Title	Crossover	ICL670
Arm/Group Description:	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.	Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight.
Overall Number of Participants Analyzed	129	266
Median (Full Range); Unit of Measure: mg/kg/day
	0.37; (0.07 to 0.78)	0.38; (-0.14 to 1.00)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	ICL670	Crossover
Arm/Group Description	Participants treated with Deferasirox (ICL670) orally once a day during the core study continued this treatment in the extension study. Dosage based on body weight.	Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight.
All-Cause Mortality
	ICL670	Crossover
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	ICL670	Crossover
	Affected / at Risk (%)	Affected / at Risk (%)
Total	102/296 (34.46%)	61/259 (23.55%)
Blood and lymphatic system disorders
Anaemia † 1	1/296 (0.34%)	2/259 (0.77%)
Anaemia haemolytic autoimmune † 1	2/296 (0.68%)	0/259 (0.00%)
Haemolysis † 1	0/296 (0.00%)	1/259 (0.39%)
Hypersplenism † 1	8/296 (2.70%)	6/259 (2.32%)
Leukopenia † 1	1/296 (0.34%)	0/259 (0.00%)
Lymphadenopathy † 1	1/296 (0.34%)	0/259 (0.00%)
Neutropenia † 1	1/296 (0.34%)	1/259 (0.39%)
Neutrophilia † 1	0/296 (0.00%)	1/259 (0.39%)
Splenomegaly † 1	5/296 (1.69%)	1/259 (0.39%)
Cardiac disorders
Arrhythmia † 1	2/296 (0.68%)	0/259 (0.00%)
Atrial flutter † 1	2/296 (0.68%)	0/259 (0.00%)
Cardiac failure † 1	1/296 (0.34%)	0/259 (0.00%)
Cardiac failure congestive † 1	1/296 (0.34%)	0/259 (0.00%)
Cardio-respiratory arrest † 1	0/296 (0.00%)	1/259 (0.39%)
Cardiogenic shock † 1	1/296 (0.34%)	0/259 (0.00%)
Myocardial infarction † 1	1/296 (0.34%)	0/259 (0.00%)
Tachycardia † 1	0/296 (0.00%)	1/259 (0.39%)
Ventricular tachycardia † 1	2/296 (0.68%)	0/259 (0.00%)
Congenital, familial and genetic disorders
Accessory spleen † 1	0/296 (0.00%)	1/259 (0.39%)
Thalassaemia beta † 1	1/296 (0.34%)	1/259 (0.39%)
Ear and labyrinth disorders
Vertigo † 1	1/296 (0.34%)	0/259 (0.00%)
Eye disorders
Cataract † 1	1/296 (0.34%)	0/259 (0.00%)
Lenticular opacities † 1	1/296 (0.34%)	1/259 (0.39%)
Papilloedema † 1	0/296 (0.00%)	1/259 (0.39%)
Vision blurred † 1	1/296 (0.34%)	0/259 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	8/296 (2.70%)	4/259 (1.54%)
Abdominal pain lower † 1	0/296 (0.00%)	1/259 (0.39%)
Abdominal pain upper † 1	2/296 (0.68%)	0/259 (0.00%)
Acute abdomen † 1	0/296 (0.00%)	2/259 (0.77%)
Appendicitis perforated † 1	0/296 (0.00%)	1/259 (0.39%)
Colitis † 1	1/296 (0.34%)	0/259 (0.00%)
Diarrhoea † 1	1/296 (0.34%)	1/259 (0.39%)
Duodenal ulcer † 1	1/296 (0.34%)	0/259 (0.00%)
Dyspepsia † 1	1/296 (0.34%)	0/259 (0.00%)
Gastric ulcer † 1	1/296 (0.34%)	0/259 (0.00%)
Gastrointestinal haemorrhage † 1	0/296 (0.00%)	1/259 (0.39%)
Ileus † 1	1/296 (0.34%)	1/259 (0.39%)
Ileus paralytic † 1	0/296 (0.00%)	1/259 (0.39%)
Inguinal hernia † 1	1/296 (0.34%)	0/259 (0.00%)
Nausea † 1	1/296 (0.34%)	0/259 (0.00%)
Oesophagitis † 1	1/296 (0.34%)	0/259 (0.00%)
Pancreatitis † 1	2/296 (0.68%)	0/259 (0.00%)
Pancreatitis acute † 1	1/296 (0.34%)	0/259 (0.00%)
Peptic ulcer † 1	2/296 (0.68%)	0/259 (0.00%)
Peritoneal haemorrhage † 1	1/296 (0.34%)	0/259 (0.00%)
Peritonitis † 1	0/296 (0.00%)	1/259 (0.39%)
Varices oesophageal † 1	0/296 (0.00%)	1/259 (0.39%)
Vomiting † 1	4/296 (1.35%)	0/259 (0.00%)
General disorders
Asthenia † 1	3/296 (1.01%)	0/259 (0.00%)
Chest pain † 1	2/296 (0.68%)	0/259 (0.00%)
Death † 1	1/296 (0.34%)	0/259 (0.00%)
Malaise † 1	1/296 (0.34%)	0/259 (0.00%)
Oedema peripheral † 1	0/296 (0.00%)	1/259 (0.39%)
Pain † 1	1/296 (0.34%)	0/259 (0.00%)
Pyrexia † 1	10/296 (3.38%)	6/259 (2.32%)
Hepatobiliary disorders
Bile duct stone † 1	0/296 (0.00%)	1/259 (0.39%)
Biliary colic † 1	1/296 (0.34%)	0/259 (0.00%)
Biliary tract disorder † 1	1/296 (0.34%)	0/259 (0.00%)
Cholangitis † 1	1/296 (0.34%)	0/259 (0.00%)
Cholecystitis † 1	1/296 (0.34%)	1/259 (0.39%)
Cholecystitis acute † 1	1/296 (0.34%)	0/259 (0.00%)
Cholecystitis chronic † 1	1/296 (0.34%)	1/259 (0.39%)
Cholelithiasis † 1	7/296 (2.36%)	6/259 (2.32%)
Cholestasis † 1	0/296 (0.00%)	1/259 (0.39%)
Hepatitis † 1	2/296 (0.68%)	0/259 (0.00%)
Hepatitis acute † 1	1/296 (0.34%)	1/259 (0.39%)
Jaundice † 1	1/296 (0.34%)	0/259 (0.00%)
Jaundice cholestatic † 1	1/296 (0.34%)	1/259 (0.39%)
Liver injury † 1	1/296 (0.34%)	0/259 (0.00%)
Infections and infestations
Acute tonsillitis † 1	1/296 (0.34%)	0/259 (0.00%)
Appendicitis † 1	1/296 (0.34%)	2/259 (0.77%)
Bronchitis † 1	3/296 (1.01%)	0/259 (0.00%)
Bronchopneumonia † 1	1/296 (0.34%)	0/259 (0.00%)
Escherichia sepsis † 1	1/296 (0.34%)	0/259 (0.00%)
Gastroenteritis † 1	1/296 (0.34%)	3/259 (1.16%)
Gastroenteritis viral † 1	1/296 (0.34%)	0/259 (0.00%)
Gastrointestinal infection † 1	1/296 (0.34%)	0/259 (0.00%)
HIV infection † 1	1/296 (0.34%)	0/259 (0.00%)
Hepatitis C † 1	0/296 (0.00%)	1/259 (0.39%)
Infection † 1	1/296 (0.34%)	0/259 (0.00%)
Infectious mononucleosis † 1	1/296 (0.34%)	0/259 (0.00%)
Lower respiratory tract infection † 1	1/296 (0.34%)	0/259 (0.00%)
Lung abscess † 1	0/296 (0.00%)	1/259 (0.39%)
Meningitis † 1	1/296 (0.34%)	0/259 (0.00%)
Meningitis bacterial † 1	1/296 (0.34%)	0/259 (0.00%)
Orchitis † 1	0/296 (0.00%)	1/259 (0.39%)
Pharyngitis † 1	2/296 (0.68%)	1/259 (0.39%)
Pharyngitis streptococcal † 1	0/296 (0.00%)	1/259 (0.39%)
Pilonidal cyst † 1	0/296 (0.00%)	1/259 (0.39%)
Pneumonia † 1	1/296 (0.34%)	1/259 (0.39%)
Pneumonia viral † 1	1/296 (0.34%)	0/259 (0.00%)
Pyelocystitis † 1	1/296 (0.34%)	0/259 (0.00%)
Pyelonephritis acute † 1	1/296 (0.34%)	0/259 (0.00%)
Septic shock † 1	2/296 (0.68%)	0/259 (0.00%)
Sinusitis † 1	1/296 (0.34%)	0/259 (0.00%)
Streptococcal bacteraemia † 1	1/296 (0.34%)	0/259 (0.00%)
Tonsillitis † 1	1/296 (0.34%)	0/259 (0.00%)
Tooth abscess † 1	1/296 (0.34%)	0/259 (0.00%)
Upper respiratory tract infection † 1	1/296 (0.34%)	0/259 (0.00%)
Urinary tract infection † 1	3/296 (1.01%)	0/259 (0.00%)
Viral infection † 1	1/296 (0.34%)	0/259 (0.00%)
Wound infection † 1	1/296 (0.34%)	0/259 (0.00%)
Yersinia infection † 1	1/296 (0.34%)	0/259 (0.00%)
Injury, poisoning and procedural complications
Ankle fracture † 1	0/296 (0.00%)	1/259 (0.39%)
Cervical vertebral fracture † 1	1/296 (0.34%)	0/259 (0.00%)
Femoral neck fracture † 1	1/296 (0.34%)	0/259 (0.00%)
Femur fracture † 1	1/296 (0.34%)	2/259 (0.77%)
Foot fracture † 1	0/296 (0.00%)	1/259 (0.39%)
Head injury † 1	1/296 (0.34%)	0/259 (0.00%)
Heat stroke † 1	1/296 (0.34%)	0/259 (0.00%)
Jaw fracture † 1	1/296 (0.34%)	0/259 (0.00%)
Ligament rupture † 1	0/296 (0.00%)	1/259 (0.39%)
Limb injury † 1	1/296 (0.34%)	0/259 (0.00%)
Lower limb fracture † 1	0/296 (0.00%)	1/259 (0.39%)
Post procedural haemorrhage † 1	1/296 (0.34%)	0/259 (0.00%)
Procedural pain † 1	2/296 (0.68%)	0/259 (0.00%)
Road traffic accident † 1	2/296 (0.68%)	1/259 (0.39%)
Tendon rupture † 1	1/296 (0.34%)	0/259 (0.00%)
Transfusion reaction † 1	2/296 (0.68%)	0/259 (0.00%)
Investigations
Alanine aminotransferase increased † 1	0/296 (0.00%)	1/259 (0.39%)
Blood creatinine increased † 1	1/296 (0.34%)	0/259 (0.00%)
Blood potassium decreased † 1	0/296 (0.00%)	1/259 (0.39%)
Blood sodium decreased † 1	0/296 (0.00%)	1/259 (0.39%)
Cardiovascular function test abnormal † 1	0/296 (0.00%)	1/259 (0.39%)
Cells in urine † 1	1/296 (0.34%)	0/259 (0.00%)
Haemoglobin decreased † 1	0/296 (0.00%)	1/259 (0.39%)
Hepatic enzyme increased † 1	1/296 (0.34%)	0/259 (0.00%)
Liver function test abnormal † 1	0/296 (0.00%)	1/259 (0.39%)
Serum ferritin increased † 1	0/296 (0.00%)	1/259 (0.39%)
Streptococcal identification test positive † 1	0/296 (0.00%)	1/259 (0.39%)
Transaminases increased † 1	3/296 (1.01%)	2/259 (0.77%)
Metabolism and nutrition disorders
Dehydration † 1	0/296 (0.00%)	1/259 (0.39%)
Diabetes mellitus † 1	1/296 (0.34%)	0/259 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/296 (0.68%)	0/259 (0.00%)
Back pain † 1	2/296 (0.68%)	1/259 (0.39%)
Bone cyst † 1	1/296 (0.34%)	0/259 (0.00%)
Bone lesion † 1	1/296 (0.34%)	0/259 (0.00%)
Bone pain † 1	1/296 (0.34%)	0/259 (0.00%)
Osteonecrosis † 1	0/296 (0.00%)	1/259 (0.39%)
Osteoporotic fracture † 1	1/296 (0.34%)	0/259 (0.00%)
Pain in extremity † 1	0/296 (0.00%)	1/259 (0.39%)
Pathological fracture † 1	1/296 (0.34%)	0/259 (0.00%)
Rheumatoid arthritis † 1	0/296 (0.00%)	1/259 (0.39%)
Spinal osteoarthritis † 1	1/296 (0.34%)	0/259 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myolipoma † 1	0/296 (0.00%)	1/259 (0.39%)
Pituitary tumour benign † 1	1/296 (0.34%)	0/259 (0.00%)
Nervous system disorders
Cerebral haemorrhage † 1	1/296 (0.34%)	0/259 (0.00%)
Cerebral ischaemia † 1	0/296 (0.00%)	1/259 (0.39%)
Cerebrovascular disorder † 1	1/296 (0.34%)	0/259 (0.00%)
Clumsiness † 1	1/296 (0.34%)	0/259 (0.00%)
Depressed level of consciousness † 1	1/296 (0.34%)	0/259 (0.00%)
Dizziness † 1	2/296 (0.68%)	0/259 (0.00%)
Epilepsy † 1	1/296 (0.34%)	0/259 (0.00%)
Headache † 1	2/296 (0.68%)	0/259 (0.00%)
Loss of consciousness † 1	1/296 (0.34%)	0/259 (0.00%)
Psychomotor hyperactivity † 1	1/296 (0.34%)	0/259 (0.00%)
Syncope † 1	1/296 (0.34%)	0/259 (0.00%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	1/296 (0.34%)	0/259 (0.00%)
Pregnancy † 1	0/296 (0.00%)	2/259 (0.77%)
Psychiatric disorders
Depression † 1	1/296 (0.34%)	0/259 (0.00%)
Dysthymic disorder † 1	0/296 (0.00%)	1/259 (0.39%)
Insomnia † 1	1/296 (0.34%)	0/259 (0.00%)
Suicide attempt † 1	1/296 (0.34%)	0/259 (0.00%)
Renal and urinary disorders
Calculus ureteric † 1	0/296 (0.00%)	1/259 (0.39%)
Calculus urinary † 1	2/296 (0.68%)	0/259 (0.00%)
Glomerulonephropathy † 1	1/296 (0.34%)	0/259 (0.00%)
Hydronephrosis † 1	1/296 (0.34%)	0/259 (0.00%)
Ketonuria † 1	0/296 (0.00%)	1/259 (0.39%)
Nephrolithiasis † 1	2/296 (0.68%)	0/259 (0.00%)
Nephropathy † 1	1/296 (0.34%)	0/259 (0.00%)
Proteinuria † 1	1/296 (0.34%)	1/259 (0.39%)
Renal colic † 1	1/296 (0.34%)	0/259 (0.00%)
Renal failure † 1	1/296 (0.34%)	0/259 (0.00%)
Renal tubular disorder † 1	0/296 (0.00%)	1/259 (0.39%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema † 1	1/296 (0.34%)	0/259 (0.00%)
Cough † 1	1/296 (0.34%)	0/259 (0.00%)
Dyspnoea † 1	1/296 (0.34%)	1/259 (0.39%)
Lung disorder † 1	1/296 (0.34%)	0/259 (0.00%)
Wheezing † 1	1/296 (0.34%)	0/259 (0.00%)
Skin and subcutaneous tissue disorders
Dermal cyst † 1	0/296 (0.00%)	1/259 (0.39%)
Dermatitis allergic † 1	1/296 (0.34%)	0/259 (0.00%)
Dyshidrosis † 1	0/296 (0.00%)	1/259 (0.39%)
Henoch-Schonlein purpura † 1	0/296 (0.00%)	1/259 (0.39%)
Hyperhidrosis † 1	1/296 (0.34%)	0/259 (0.00%)
Rash † 1	2/296 (0.68%)	0/259 (0.00%)
Surgical and medical procedures
Cholecystectomy † 1	1/296 (0.34%)	0/259 (0.00%)
Splenectomy † 1	2/296 (0.68%)	1/259 (0.39%)
Vascular disorders
Deep vein thrombosis † 1	1/296 (0.34%)	0/259 (0.00%)
Hypotension † 1	1/296 (0.34%)	0/259 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	ICL670	Crossover
	Affected / at Risk (%)	Affected / at Risk (%)
Total	266/296 (89.86%)	236/259 (91.12%)
Cardiac disorders
Palpitations † 1	17/296 (5.74%)	11/259 (4.25%)
Ear and labyrinth disorders
Ear pain † 1	16/296 (5.41%)	14/259 (5.41%)
Gastrointestinal disorders
Abdominal pain † 1	74/296 (25.00%)	57/259 (22.01%)
Abdominal pain upper † 1	51/296 (17.23%)	52/259 (20.08%)
Constipation † 1	17/296 (5.74%)	13/259 (5.02%)
Diarrhoea † 1	68/296 (22.97%)	73/259 (28.19%)
Dyspepsia † 1	21/296 (7.09%)	17/259 (6.56%)
Nausea † 1	62/296 (20.95%)	52/259 (20.08%)
Toothache † 1	22/296 (7.43%)	14/259 (5.41%)
Vomiting † 1	72/296 (24.32%)	61/259 (23.55%)
General disorders
Asthenia † 1	29/296 (9.80%)	31/259 (11.97%)
Fatigue † 1	29/296 (9.80%)	22/259 (8.49%)
Influenza like illness † 1	12/296 (4.05%)	17/259 (6.56%)
Oedema peripheral † 1	17/296 (5.74%)	15/259 (5.79%)
Pyrexia † 1	110/296 (37.16%)	108/259 (41.70%)
Hepatobiliary disorders
Cholelithiasis † 1	18/296 (6.08%)	5/259 (1.93%)
Infections and infestations
Acute tonsillitis † 1	28/296 (9.46%)	21/259 (8.11%)
Bronchitis † 1	42/296 (14.19%)	41/259 (15.83%)
Ear infection † 1	22/296 (7.43%)	7/259 (2.70%)
Gastroenteritis † 1	37/296 (12.50%)	29/259 (11.20%)
Influenza † 1	70/296 (23.65%)	65/259 (25.10%)
Nasopharyngitis † 1	73/296 (24.66%)	56/259 (21.62%)
Pharyngitis † 1	54/296 (18.24%)	57/259 (22.01%)
Rhinitis † 1	52/296 (17.57%)	45/259 (17.37%)
Sinusitis † 1	21/296 (7.09%)	13/259 (5.02%)
Tonsillitis † 1	29/296 (9.80%)	22/259 (8.49%)
Tooth abscess † 1	15/296 (5.07%)	8/259 (3.09%)
Upper respiratory tract infection † 1	52/296 (17.57%)	32/259 (12.36%)
Urinary tract infection † 1	23/296 (7.77%)	14/259 (5.41%)
Injury, poisoning and procedural complications
Transfusion reaction † 1	32/296 (10.81%)	36/259 (13.90%)
Investigations
Blood creatinine increased † 1	46/296 (15.54%)	22/259 (8.49%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	44/296 (14.86%)	39/259 (15.06%)
Back pain † 1	59/296 (19.93%)	49/259 (18.92%)
Bone pain † 1	15/296 (5.07%)	14/259 (5.41%)
Musculoskeletal pain † 1	15/296 (5.07%)	4/259 (1.54%)
Osteoporosis † 1	17/296 (5.74%)	15/259 (5.79%)
Pain in extremity † 1	30/296 (10.14%)	20/259 (7.72%)
Nervous system disorders
Headache † 1	84/296 (28.38%)	81/259 (31.27%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	110/296 (37.16%)	85/259 (32.82%)
Epistaxis † 1	8/296 (2.70%)	14/259 (5.41%)
Nasal congestion † 1	10/296 (3.38%)	14/259 (5.41%)
Oropharyngeal pain † 1	62/296 (20.95%)	50/259 (19.31%)
Productive cough † 1	15/296 (5.07%)	12/259 (4.63%)
Skin and subcutaneous tissue disorders
Rash † 1	33/296 (11.15%)	24/259 (9.27%)
Urticaria † 1	23/296 (7.77%)	14/259 (5.41%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cappellini MD, Bejaoui M, Agaoglu L, Canatan D, Capra M, Cohen A, Drelichman G, Economou M, Fattoum S, Kattamis A, Kilinc Y, Perrotta S, Piga A, Porter JB, Griffel L, Dong V, Clark J, Aydinok Y. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood. 2011 Jul 28;118(4):884-93. doi: 10.1182/blood-2010-11-316646. Epub 2011 May 31. Erratum In: Blood. 2011 Nov 3;118(18):5060.

• Responsible Party: External Affairs, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00171210
• Other Study ID Numbers: CICL670A0107E1
• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Results First Submitted: December 14, 2010
• Results First Posted: May 2, 2011
• Last Update Posted: May 30, 2011